BACKGROUND: Chronic suppurative otitis media (CSOM), sometimes referred to as chronic otitis media (COM), is a chronic inflammation and often polymicrobial infection of the middle ear and mastoid cavity, characterised by ear discharge (otorrhoea) through a perforated tympanic membrane. The predominant symptoms of CSOM are ear discharge and hearing loss. Systemic antibiotics are commonly used to treat people with CSOM. This is the first update to the review published in 2021, and is one of a suite of seven Cochrane reviews evaluating the effects of non-surgical interventions for CSOM. OBJECTIVES: To assess the effects of systemic antibiotics compared to placebo, no treatment, or another systemic antibiotic in people with chronic suppurative otitis media (CSOM). SEARCH METHODS: We searched the Cochrane Ear, Nose, and Throat Register, CENTRAL, MEDLINE, Embase, four other databases, and two clinical trials registers to 15 June 2022. SELECTION CRITERIA: We included randomised controlled trials comparing systemic antibiotics (oral, injection) to placebo/no treatment or other systemic antibiotics with at least a one-week follow-up period, involving people with chronic (at least two weeks) ear discharge of unknown cause or due to CSOM. Other treatments were allowed if both treatment and control arms received it. DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were: resolution of ear discharge or 'dry ear' (whether otoscopically confirmed or not, measured at between one week and up to two weeks, two weeks to up to four weeks, and after four weeks); health-related quality of life using a validated instrument; and ear pain (otalgia)/discomfort/local irritation. Secondary outcomes included hearing, serious complications, and ototoxicity measured in several ways. We used GRADE to assess the certainty of the evidence for each outcome. MAIN RESULTS: This update found three new studies (390 participants). Overall, we included 21 studies (2525 participants). We report four core comparisons below, and describe an additional four in the Results section of the review. 1. Systemic antibiotics versus no treatment/placebo It is very uncertain from a single study if there is a difference between systemic (intravenous) antibiotics and placebo in the resolution of ear discharge between one and two weeks (risk ratio (RR) 8.47, 95% confidence interval (CI) 1.88 to 38.21; 1 study, 33 participants; very low-certainty evidence). The study did not report results for resolution of ear discharge after two weeks, or health-related quality of life. The evidence is very uncertain for hearing and serious (intracranial) complications. The study did not report ear pain and suspected ototoxicity. 2. Systemic antibiotics versus no treatment/placebo (both study arms received topical antibiotics) Seven studies assessed this comparison, with five presenting usable data. There may be little or no difference between oral ciprofloxacin and placebo/no treatment (with all participants receiving ciprofloxacin ear drops) in the resolution of ear discharge between one and two weeks (RR 1.05, 95% CI 0.94 to 1.17; I = 0%; 3 studies, 300 participants; low-certainty evidence), with similar results at two to four weeks. One study reported outcomes beyond four weeks, but the results were not usable. No studies reported health-related quality of life. The evidence is very uncertain for ear pain, serious complications, and suspected ototoxicity. 3. Systemic antibiotics versus no treatment/placebo (plus topical antibiotics and topical steroids in both study arms) Two studies used topical antibiotics plus topical steroids as background treatment in both arms. It is very uncertain if there is a difference in resolution of ear discharge between metronidazole and placebo at two to four weeks (RR 0.91, 95% CI 0.51 to 1.65; 1 study, 30 participants). This study did not report other outcomes. It is also very uncertain if co-trimoxazole improved resolution of ear discharge after four weeks compared to placebo (RR 1.54, 95% CI 1.09 to 2.16; 1 study, 98 participants; very low-certainty evidence). From the narrative reporting of one study, there was no evidence of a difference between groups for health-related quality of life, hearing, or serious complications (very low-certainty evidence). 4. Systemic antibiotics versus no treatment/placebo (plus topical antiseptics in both study arms) One study (136 participants) used topical antiseptics as background treatment in both arms, and found no difference in the resolution of ear discharge between the amoxicillin and no-treatment groups at three to four months (RR 1.03, 95% CI 0.75 to 1.41; 136 participants; very low-certainty evidence). The narrative report indicated no evidence of differences in hearing or suspected ototoxicity (very low-certainty evidence). The study reported no other outcomes. Limitations include heterogeneity in the duration and definition of CSOM used by studies included in the review. Although we planned subgroup analyses for different participant characteristics, treatment duration, and spectrum of antibiotic activity, we did not perform these analyses due to lack of available data. AUTHORS' CONCLUSIONS: The evidence available to determine whether systemic antibiotics are effective in achieving resolution of ear discharge in people with CSOM is limited. We are very uncertain if systemic antibiotics, when used alone (with or without aural toileting (ear cleaning)), are more effective than placebo or no treatment. When added to an intervention such as topical antibiotics, there may be little or no difference in resolution of ear discharge (very low-certainty evidence). Data were only available for certain classes of antibiotics; it is very uncertain whether one class of systemic antibiotic is more effective than another. Harmful effects of systemic antibiotics were poorly reported in the included studies.